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Functional studies of KDM5 family proteins

We use a range of genetic, molecular and biochemical approaches to understand how KDM5 regulates transcription. 

KDM5 function in neuronal development and function

Using Drosophila, we can combine analyses of KDM5 binding, changes to transcription and alterations in neuronal structure and function. We have shown that KDM5 regulates transcriptional programs important for the proper development and function of the glutamatergic neuromuscular junction and also the adult mushroom body. Current projects are aimed at understanding how changes to KDM5 that are associated with intellectual disability alter its molecular functions.  


Essential functions of KDM5 during development

In contrast to human cells, Drosophila has a single kdm5 gene. We have shown that loss of kdm5 leads to lethality and that this essential function of KDM5 is independent of its well-characterized histone demethylase activity. Current projects are aimed at determining how KDM5 regulates transcription independently of its histone demethylase activity. Because we have shown that KDM5 plays essential roles in a neuroendocrine tissue called the prothoracic gland, we focus primarily on this tissue. 


Human KDM5C function in organoids

To understand KDM5C function in a human cell context, we have begun iPSC-induced cerebral organoids. This project is a collaboration with Dr. Lachman's lab and the Rose F. Kennedy Intellectual and Developmental Disabilities Research Center (IDDRC) at Einstein. 

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